Reflex Human Immunodeficiency Virus (HIV) Type 1 RNA Testing Enables Timely Differentiation of False-Positive Results From Acute HIV Infection.

Accurate, timely human immunodeficiency virus (HIV) diagnosis is critical. Routine HIV screening program data were examined before and after reflex HIV type 1 RNA testing. Reflex testing facilitated confirmation of reactive HIV screening assays (as true or false positives) (odds ratio, 23.7 [95% confidence interval, 6.7-83.4]; P < .0001), improving detection of acute HIV and reducing unconfirmed discordant results.

Concurrent Testing for COVID-19 and HIV Infection at 6 High-Volume Emergency Departments in a Priority Jurisdiction for Ending the HIV Epidemic in the United States.

BACKGROUND: The COVID-19 pandemic caused disruptions in access to routine HIV screening. SETTING: We assess HIV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing across 6 emergency departments (EDs) in Cook County, Illinois. METHODS: We retrospectively analyzed the number of SARS-CoV-2 tests, HIV screens, and the proportion of concurrent tests (encounters with both SARS-CoV-2 and HIV testing), correlating with diagnoses of new and acute HIV infection. RESULTS: Five sites reported data from March 1, 2020, to February 28, 2021, and 1 site from September 1, 2020, to February 28, 2021. A total of 1,13,645 SARS-CoV-2 and 36,094 HIV tests were performed; 17,469 of these were concurrent tests. There were 102 new HIV diagnoses, including 25 acute infections. Concurrent testing proportions ranged from 6.7% to 37% across sites (P < 0.001). HIV testing volume correlated with the number of new diagnoses (r = 0.66, P < 0.01). HIV testing with symptomatic SARS-CoV-2 testing was strongly correlated with diagnosis of acute infections (r = 0.87, P < 0.001); this was not statistically significant when controlling for HIV testing volumes (r = 0.59, P = 0.056). Acute patients were more likely to undergo concurrent testing (21/25) versus other new diagnoses (29/77; odds ratio = 8.69, 95% CI: 2.7 to 27.8, P < 0.001). CONCLUSIONS: Incorporating HIV screening into SARS-CoV-2 testing in the ED can help maintain HIV screening volumes. Although all patients presenting to the ED should be offered opt-out HIV screening, testing individuals with symptoms of COVID-19 or other viral illness affords the opportunity to diagnose symptomatic acute and early HIV infection, rapidly link to care, and initiate treatment.

Utility of the Signal-to-Cutoff Ratio and Antigen Index from Fourth- and Fifth-Generation HIV-1/HIV-2 Antigen/Antibody Assays for the Diagnosis of Acute HIV Infection: Applicability for Real-Time Use for Immediate Initiation of Antiretroviral Therapy.

Identification of individuals with acute HIV infection (AHI) and rapid initiation of antiretroviral therapy (ART) are priorities for HIV elimination efforts. Fourth- and fifth-generation HIV-1/HIV-2 antigen (Ag)/antibody (Ab) combination assays can quickly identify patients with AHI, but false-positive results can occur. Confirmatory nucleic acid amplification testing (NAAT) may not be rapidly available. We reviewed the data for 127 patients with positive fourth-generation ARCHITECT and fifth-generation Bio-Plex immunoassay results who had negative or indeterminate confirmatory Ab testing results, which yielded 38 patients with confirmed AHI and 89 patients with false-positive results. The receiver operating characteristic (ROC) curves showed excellent discriminatory power, with an area under the curve (AUC) for the signal-to-cutoff (S/CO) ratio of 0.970 (95% confidence interval [CI], 0.935 to 1.00) and an AUC for the Ag index (AI) of 0.968 (95% CI, 0.904 to 1.00). A threshold of 3.78 for the S/CO ratio would maximize the sensitivity (96.3%) and specificity (93.4%). The threshold for AI was 2.83 (sensitivity of 100% and specificity of 96.4%). The S/CO ratio was significantly correlated with the viral load (Spearman correlation coefficient, 0.486 [P = 0.014]), but the AI was not. The viral loads were all high, with a median of >2.8 million copies/mL. Two false-positive results with AI and S/CO ratio values markedly higher than the medians were observed, indicating that biological false-positive results can occur. Review of the S/CO ratio or AI may be used to improve the accuracy of AHI diagnosis prior to confirmatory NAAT results being available.

Partner Notification Services for Patients with Established and New HIV Infection Leads to Diagnosis and Linkage of HIV-Positive Partners.

Offering people living with HIV the opportunity to refer partners for HIV testing is an efficient way of identifying new HIV diagnoses. This report describes the outcomes of physician-led partner services at an urban academic center. Patients with HIV VL > 1000 copies/mL in both inpatient and outpatient settings were offered partner notification services (PNS). Of referred partners, 8.7% had a new diagnosis of HIV. New HIV+ partners were as likely to be referred by patients with existing HIV diagnoses as new diagnoses (p = 0.61), and as likely to be referred by patients interviewed while hospitalized as those in the clinic (p = 0.61).

Bacterial infections in lung transplantation.

Lung transplantation has lower survival rates compared to other than other solid organ transplants (SOT) due to higher rates of infection and rejection-related complications, and bacterial infections (BI) are the most frequent infectious complications. Excess morbidity and mortality are not only a direct consequence of these BI, but so are subsequent loss of allograft tolerance, rejection, and chronic lung allograft dysfunction due to bronchiolitis obliterans syndrome (BOS). A wide variety of pathogens can cause infections in lung transplant recipients (LTRs), including a number of nosocomial pathogens and other multidrug-resistant (MDR) pathogens. Although pneumonia and intrathoracic infections predominate, LTRs are at risk of a number of types of infections. Risk factors include altered anatomy and function of airways, impaired immunity, the microbial flora of the donor and recipient, underlying medical conditions, and genetic factors. Further work on immune monitoring has the potential to improve outcomes. The infecting agents can be derived from the donor lung, pre-existing recipient flora, or acquired from the environment over time. Certain infections may preclude lung transplantation, but this varies from center to center, and more recent studies suggest fewer patients should be disqualified. New molecular methods allow microbiome studies of the lung, gut, and other sites that may further our knowledge of how airway colonization can result in infection and allograft loss. Surveillance, early diagnosis, and aggressive antimicrobial therapy of BI is critical in LTRs. Antibiotic resistance is a major barrier to successful management of these infections. The availability of new agents for MDR Gram-negatives may improve outcomes. Other new therapies, such as bacteriophage therapy, show promise for the future. Finally, it is important to prevent infections through peri-transplant prophylaxis, vaccination, and infection control measures.

Community-acquired Coinfection in Coronavirus Disease 2019: A Retrospective Observational Experience.

Community-acquired coinfection in coronavirus disease 2019 (COVID-19) is not well defined. Current literature describes coinfection in 0-40% of COVID-19 patients. In this retrospective report, coinfection was identified in 3.7% of patients and 41% of patients admitted to intensive care (P < .005). Despite infrequent coinfection, antibiotics were used in 69% of patients.

Late onset infectious complications and safety of tocilizumab in the management of COVID-19.

BACKGROUND: Tocilizumab (TCZ) has been used in the management of COVID-19-related cytokine release syndrome (CRS). Concerns exist regarding the risk of infections and drug-related toxicities. We sought to evaluate the incidence of these TCZ complications among COVID-19 patients. METHODS: All adult inpatients with COVID-19 between 1 March and 25 April 2020 that received TCZ were included. We compared the rate of late-onset infections (>48 hours following admission) to a control group matched according to intensive care unit admission and mechanical ventilation requirement. Post-TCZ toxicities evaluated included: elevated liver function tests (LFTs), GI perforation, diverticulitis, neutropenia, hypertension, allergic reactions, and infusion-related reactions. RESULTS: Seventy-four patients were included in each group. Seventeen infections in the TCZ group (23%) and 6 (8%) infections in the control group occurred >48 hours after admission (P = .013). Most infections were bacterial with pneumonia being the most common manifestation. Among patients receiving TCZ, LFT elevations were observed in 51%, neutropenia in 1.4%, and hypertension in 8%. The mortality rate among those that received TCZ was greater than the control (39% versus 23%, P = .03). CONCLUSION: Late onset infections were significantly more common among those receiving TCZ. Combining infections and TCZ-related toxicities, 61% of patients had a possible post-TCZ complication. While awaiting clinical trial results to establish the efficacy of TCZ for COVID-19 related CRS, the potential for infections and TCZ related toxicities should be carefully weighed when considering use.

IL-6 Inhibition in Critically Ill COVID-19 Patients Is Associated With Increased Secondary Infections.

Background: Anti-inflammatory therapies such as IL-6 inhibition have been proposed for COVID-19 in a vacuum of evidence-based treatment. However, abrogating the inflammatory response in infectious diseases may impair a desired host response and pre-dispose to secondary infections. Methods: We retrospectively reviewed the medical record of critically ill COVID-19 patients during an 8-week span and compared the prevalence of secondary infection and outcomes in patients who did and did not receive tocilizumab. Additionally, we included representative histopathologic post-mortem findings from several COVID-19 cases that underwent autopsy at our institution. Results: One hundred eleven patients were identified, of which 54 had received tocilizumab while 57 had not. Receiving tocilizumab was associated with a higher risk of secondary bacterial (48.1 vs. 28.1%; p = 0.029 and fungal (5.6 vs. 0%; p = 0.112) infections. Consistent with higher number of infections, patients who received tocilizumab had higher mortality (35.2 vs. 19.3%; p = 0.020). Seven cases underwent autopsy. In three cases who received tocilizumab, there was evidence of pneumonia on pathology. Of the four cases that had not been given tocilizumab, two showed evidence of aspiration pneumonia and two exhibited diffuse alveolar damage. Conclusions: Experimental therapies are currently being applied to COVID-19 outside of clinical trials. Anti-inflammatory therapies such as anti-IL-6 therapy have the potential to impair viral clearance, pre-dispose to secondary infection, and cause harm. We seek to raise physician awareness of these issues and highlight the need to better understand the immune response in COVID-19.

Automatic ID Consultation for Inpatients With COVID-19: Point, Counterpoint, and a Single-Center Experience.

There are many unknowns with regard to COVID-19 clinical management, including the role of Infectious Diseases Consultation (IDC). As hospitalizations for COVID-19 continue, hospitals are assessing how to optimally and efficiently manage COVID-19 inpatients. Typically, primary teams must determine when IDC is appropriate, and ID clinicians provide consultation upon request of the primary team. IDC has been shown to be beneficial for many conditions; however, the impact of IDC for COVID-19 is unknown. Herein, we discuss the potential benefits and pitfalls of automatic IDC for COVID-19 inpatients. Important considerations include the quality of care provided, allocation and optimization of resources, and clinician satisfaction. Finally, we describe how automatic IDC changed throughout the COVID-19 pandemic at a single academic medical center.

Comparison of effectiveness and cost for different HIV screening strategies implemented at large urban medical centre in the United States.

INTRODUCTION: Incident HIV infections persist in the United States (U.S.) among marginalized populations. Targeted and cost-efficient testing strategies can help in reaching HIV elimination. This analysis compares the effectiveness and cost of three HIV testing strategies in a high HIV burden area in the U.S. in identifying new HIV infections. METHODS: We performed a cost analysis comparing three HIV testing strategies in Chicago: (1) routine screening (RS) in an inpatient and outpatient setting, (2) modified partner services (MPS) among networks of the recently HIV infected and diagnosed, and (3) a respondent drive sampling (RDS)-based social network (SN) approach targeting young African-American men who have sex with men. All occurred at the same academic medical centre during the following times: routine testing, 2011 to 2016; MPS, 2013 to 2016; SN: 2013 to 2014. Costs were in 2016 dollars and included personnel, HIV testing, training, materials, overhead. Outcomes included cost per test, HIV-positive test and new diagnosis. Sensitivity analyses were performed to assess the impact of population demographics. RESULTS: The RS programme completed 57,308 HIV tests resulting in 360 (0.6%) HIV-positive tests and 165 new HIV diagnoses (0.28%). The MPS completed 146 HIV tests, resulting in 79 (54%) HIV-positive tests and eight new HIV diagnoses (5%). The SN strategy completed 508 HIV tests, resulting in 210 (41%) HIV-positive tests and 37 new HIV diagnoses (7.2%). Labour accounted for the majority of costs in all strategies. The estimated cost per new HIV diagnosis was $16,773 for the RS programme, $61,418 for the MPS programme and $15,683 for the SN testing programme. These costs were reduced for the RS and MPS strategies in sensitivity analyses limiting testing efficacy to the highest prevalence patient populations ($2,841 and $33,233 respectively). CONCLUSIONS: The SN strategy yielded the highest proportion of new diagnoses, followed closely by the MPS programme. Both the SN strategy and RS programme were comparable in the cost per new diagnosis. A simultaneous approach that consists of RS in combination with SN testing may be most effective for identifying new HIV infections in settings with heterogeneous epidemics with both high rates of HIV prevalence and HIV testing.

IL6 inhibition in critically ill COVID-19 patients is associated with increased secondary infections.

BACKGROUND: Anti-inflammatory therapies such as IL-6 inhibition have been proposed for COVID-19 in a vacuum of evidence-based treatment. However, abrogating the inflammatory response in infectious diseases may impair a desired host response and predispose to secondary infections. METHODS: We retrospectively reviewed the medical record of critically ill COVID-19 patients during an 8-week span and compared the prevalence of secondary infection and outcomes in patients who did and did not receive tocilizumab. Additionally, we included representative histopathologic post-mortem findings from several COVID-19 cases that underwent autopsy at our institution. RESULTS: 111 patients were identified, of which 54 had received tocilizumab while 57 had not. Receiving tocilizumab was associated with a higher risk of secondary bacterial (48.1% vs. 28.1%, p=0.029 and fungal (5.6% vs. 0%, p=0.112) infections. Consistent with higher number of infections, patients who received tocilizumab had higher mortality (35.2% vs. 19.3%, p=0.020). Seven cases underwent autopsy. In 3 cases who received tocilizumab, there was evidence of pneumonia on pathology. Of the 4 cases that had not been given tocilizumab, 2 showed evidence of aspiration pneumonia and 2 exhibited diffuse alveolar damage. CONCLUSIONS: Experimental therapies are currently being applied to COVID-19 outside of clinical trials. Anti-inflammatory therapies such as anti-IL-6 therapy have the potential to impair viral clearance, predispose to secondary infection, and cause harm. We seek to raise physician awareness of these issues and highlight the need to better understand the immune response in COVID-19.

Implementing Rapid Initiation of Antiretroviral Therapy for Acute HIV Infection Within a Routine Testing and Linkage to Care Program in Chicago.

Growing evidence suggests that rapid initiation of antiretroviral therapy for HIV improves care continuum outcomes. We evaluated process and clinical outcomes for rapid initiation in acute HIV infection within a multisite health care-based HIV testing and linkage to care program in Chicago. Through retrospective analysis of HIV testing data (2016-2017), we assessed linkage to care, initiation of antiretroviral therapy, and viral suppression. Of 334 new HIV diagnoses, 33 (9.9%) individuals had acute HIV infection. Median time to linkage was 11 (interquartile range [IQR]: 5-19.5) days, with 15 days (IQR 5-27) to initiation of antiretroviral therapy. Clients achieved viral suppression at a median of 131 (IQR: 54-188) days. Of all, 69.7% were retained in care, all of whom were virally suppressed. Sites required few additional resources to incorporate rapid initiation into existing processes. Integration of rapid initiation of antiretroviral therapy into existing HIV screening programs is a promising strategy for scaling up this important intervention.

A Case Series of Five People Living with HIV Hospitalized with COVID-19 in Chicago, Illinois.

The risk of COVID-19 among people living with HIV (PLWH) is largely unknown and there have been very few reported cases in the literature. We report a case series of five PLWH with COVID-19. We identified all patients with a diagnosis of HIV who tested positive for SARS-CoV-2 at University of Chicago Medicine between March 1, 2020, and April 7, 2020. We retrospectively collected data regarding demographics, comorbidities, medications, laboratory test results, radiology results, and outcomes associated with COVID-19. All five PLWH with COVID-19 were African American; 80% (4/5) were cisgender females. The mean age of patients was 48 years old (range 38-53). The majority of patients presented with cough, fever, and shortness of breath. Three patients had diarrhea. One patient presented with predominantly cardiac symptoms. All were taking antiretroviral therapy (ART) with CD4 count >200 cells/mm3 and suppressed HIV viral loads at the time of COVID-19 diagnosis. All five patients were hospitalized, two required supplemental oxygen, and none required mechanical ventilation. Four patients were treated with azithromycin and a cephalosporin and two were also treated with hydroxychloroquine. The median length of stay was 3 days (range 2-7). All patients recovered. More research is needed to understand the risks of COVID-19 among PLWH and the impact of ART on outcomes for patients with COVID-19.

Acquired hypogammaglobulinemia and pathogen-specific antibody depletion after solid organ transplantation in human immunodeficiency virus infection: A brief report.

Hypogammaglobulinemia (HGG) frequently occurs in recipients after types of (SOT). The incidence and significance of HGG in HIV+ recipients of SOT are just being explored. We reported that 12% of the recipients in the SOT in multi-center HIV-TR (HIV-TR) Study developed moderate or severe HGG at 1 year. In LT recipients, this was associated with serious infections and death. We have now further characterized the decreased antibodies in HIV+ SOT recipients who developed HGG. We measured the levels of pathogen-specific antibodies and poly-specific self-reactive antibodies (PSA) in relation to total IgG levels from serial serum samples for 20 HIV+ SOT recipients who developed moderate to severe HGG following SOT. Serum antibody levels to measles, tetanus toxoid, and HIV-1 were determined by EIA. Levels of PSAs were determined by incubating control lymphocytes with patient serum, staining with anti-human IgG Fab-FITC, and analysis by flow cytometry. Levels of PSA were higher compared to healthy, HIV-uninfected controls at pre-transplant baseline and increased by weeks 12 and 26, but the changes were not significant. Likewise, anti-HIV antibody levels remained unchanged over time. In contrast, antibody levels against measles and tetanus were significantly reduced from baseline by week 12, and did not return to baseline, even after 2 years. For HIV patients who develop moderate to severe HGG after transplant, the reduction in IgG levels is associated with a significant decrease in pathogen-specific antibody titers, while PSA levels and anti-HIV antibodies are unchanged. This may contribute to infectious complications and other clinical endpoints.

A Clinical Informatics Approach to Reengagement in HIV Care in the Emergency Department.

Emergency department visits provide an opportunity to reengage people living with HIV (PLWH) who are out of care. We developed an electronic medical record-based algorithm to identify PLWH in the emergency department and inpatient settings and utilized a trained HIV care navigator to reengage PLWH in these settings. The algorithm identified 420 PLWH during the 14-month observation period. Of these, 56 patients were out of care. Out-of-care individuals were significantly younger than those in care (mean age: 38.6 ± 15.5 vs 46.3 ±14.8 years, P < .001) and more likely to be uninsured (7.1% [4/56] vs 1.8% [6/337], P = .02). Among out-of-care patients, 66.1% (37/56) were reengaged in care. Only 21.4% (12/56) of out-of-care patients had previously received outpatient HIV care at our institution. This project demonstrates the feasibility of using an electronic medical record alert and HIV care navigator to reengage PLWH seeking emergency medical care.